Photodynamic therapy (PDT), a recently developed method of intervention in the treatment of cancer, is based on the systemic administration of certain photosensitizing dyes, e.g. psoralens, pthalocyanins, acridine orange, and porphyrins in a manner that results in their selective accumulation into rapidly-proliferating cancer cells and the subsequent exposure of the tumor to light from a tunable laser, to kill the tumor (1,2). The dyes, due to their photosensizing nature, capture photons from the light and transfer the energy to a neighboring oxygen molecule. This secondary reaction converts oxygen molecules to highly cytotoxic singlet oxygen, which leads to the death of the tumor cells. Since the irradiation is carried out at a wavelength of 600–800 nm, and singlet oxygen can travel only 0.1–0.2 μm from its site of generation, little damage occurs to the surrounding healthy tissues.
The above description, however, is somewhat of an idealized situation because (a) selective accumulation of the PDT dyes solely by tumor cells is often difficult to achieve, (b) normal cells are also capable of accumulating porphyrins, and (c) the excretion of porphyrins from tissue is often slow. Clinically, these problems are often countered by the administration of a high dose of the dye, which can cause killing of the healthy cells surrounding the malignant tissues and prolonged toxicity of large body areas toward light-exposure.
Despite these problems, PDT has been applied to malignancies of esophagus (3), bladder (4), eye (5,6), and skin (7,8) with very encouraging results. A positive response to PDT that lasted at least four months was achieved in treatment of a malignancy of the eye (6). Additionally, response rates of up to 80% have been observed in basal cell carcinomas (9,10). In a recent study involving an EMT-6 mammary tumor model, a 100% cure rate was observed using a combination of PDT dyes (2). The porphyrin dye Photofrin is an FDA-approved agent for PDT of cancers of esophagus, lung and skin (11). Several other dyes are currently under different phases of clinical studies for various cancers (12).
However, in regard to breast cancer, PDT has so far been used only in recurrent cases, with moderate success (13–17). It was observed that, although tumor nodules in the focal area could be controlled by PDT, new lesions appeared outside the area of treatment (17). It is likely that non-specific distribution of the PDT dye leads to only partial cytotoxicity and resultant cell-death. Thus, new methods of exploiting PDT to effectively combat a wide variety of cancers, especially breast cancer, would be particularly welcome.